Declarative or episodic memory systems based in the hippocampus and medial temporal lobes are specialized for rapid reorientation to new contexts, supporting appropriately rapid shifts in behavior. Surprisingly, the potential for leveraging these mechanisms in cognitive therapy remains untapped. We have demonstrated that increased fMRI activation of declarative memory systems together with dopaminergic midbrain during reward anticipation correlates with memory encoding for upcoming experience. Our findings suggest a method and mechanism for using "behavioral neurostimulation" of dopaminergic systems to prime the hippocampus for learning. This approach contrasts with conventional paradigms in psychopharmacology where the goal is chronic equilibrium of neuromodulatory systems. Here, the adjustment is explicitly targeted to the period of learning. We propose three series of experiments designed to 1) to test the existence of a causal relationship between mesolimbic activation per se and memory encoding success using real-time fMRI;2) to demonstrate the suitability of this phenomenon to clinical interventions;and 3) determine long-term effects on behavior from the impact of a single salient episode in a therapeutic session. We expect these studies to provide a foundation for using cognitive and behavioral regulation of dopamine systems to prepare the brain for adaptive learning. PUBLIC HEALTH RELEVANCE: We propose to enhance learning during cognitive therapy by increasing the release of dopamine, a neurotransmitter known to enhance learning and new memory formation, during the specific time period of a cognitive therapy session. We plan to stimulate dopamine systems behaviorally, prior to therapy. We expect these studies to guide the development of non-drug, individually tailored treatments to enhance learning-based therapies in psychiatry.